Controlled assembly of biodegradable gold nanoclusters for in vivo imaging

Gold nanoparticles are of interest in biomedical imaging applications due to their inert nature and ability to exhibit surface plasmon resonance. These phenomena can result in high near-infrared extinction (NIR) due to asymmetry or close interparticle spacings within gold structures, making these materials ideal for photoacoustic imaging. Using this imaging modality, these materials allow for high contrast compared to the body’s tissues which exhibit a transparent “window” between 700-1100 nm, making them perfect for early cancer detection. However many gold structures designed for this application fail to achieve high NIR-absorbance at the <5 nm sizes which are required for efficient kidney clearance. Therefore, we designed a system which assembles ~4 nm primary gold particles into closely-spaced clusters of controlled size using a biodegradable, weakly adsorbing polymer and balance of colloidal attractive and repulsive forces. Thus, when the polymer degrades in acidic environments – such as within cells – the residual charge on the primary particles leads to dissociation of the clusters back to renal-clearable constituents. Since proteins in the blood and cells can increase the diameter of the primary particles above the 5 nm threshold, nanoparticle surfaces were designed to have a mixture of charged and zwitterionic molecules to limit protein interactions through buried charges and increased particle hydration. Strongly-bound, zwitterionic thiol-containing ligands were also investigated to resist the intracellular exchange of biomolecules which could compromise the clearable nature of the particles. These decorated nanoparticles were then assembled into clusters through one of two methods which varied either gold and polymer concentrations through evaporation, or particle charge via electrolyte addition prior to quenching by dilution in DI water. Once assembled, clusters assembled with polymer showed dissociation behavior after incubation in pH 5 acidic solutions to mimic the cellular pH environment. In other cases, sintering of the gold nanoparticle clusters prevented such dissociation. This thesis demonstrates the ability to not only create biocompatible nanoparticle surfaces, but to establish control size control over nanocluster assemblies which are capable of being used as NIR contrast agents.